tbuckley/cabot-search huggingface dataset:
A simple clinical score to stratify the risk of procedure-related adverse events in ERCP procedures with trainee involvement
Authors: Theodor A. Voiosu, Andreea Benguș, Michiel Bronswijk, Ivan Lyutakov, Ivo Klarin, Bianca Voiosu, Paul Bălănescu, Claudia Diaconu, Bogdan Busuioc, Ivo Boskoski, Andrei M. Voiosu, Radu B. Mateescu, Sachin Wani
Journal: Endoscopy (2023)

BACKGROUND : Optimal training strategies in endoscopic retrograde cholangiopancreatography (ERCP) remain controversial despite the shift toward competence-based training models, with limited data available on patient safety during training. We aimed to assess whether pre-procedural clinical predictors could identify patients at low risk of developing procedure-related adverse-events (AEs) in a training environment. METHODS : We performed a prospective, multicenter, cohort study in five training centers. A data collection system documenting indication, clinical data, trainee performance (assessed using a validated competence assessment tool), technical outcomes, and AEs over a 30-day follow-up was utilized. We developed a clinical risk score (Trainee Involvement in ERCP Risk Score [TIERS]) for patients undergoing ERCP and compared the rate of AEs in a training environment between low-risk and high-risk groups. The association between trainee performance and AE rate was also evaluated. RESULTS : 1283 ERCPs (409 [31.9 %, 95 %CI 29.3 %-34.4 %] with trainee involvement) performed by 11 trainers and 10 trainees were analyzed. AEs were more frequent in the high-risk compared with the low-risk group: 26.7 % (95 %CI 20.5 %-34.7 %) vs. 17.1 % (95 %CI 12.8 %-22.2 %). TIERS demonstrated a high negative predictive value for AEs (82.9 %, 95 %CI 79.4 %-85.8 %) and was the only predictor of AEs on multivariable analysis (odds ratio 1.38, 95 %CI 1.09-1.75). Suboptimal trainee performance was associated with an increase in AE rates. CONCLUSION : Simple, clinical-based predictive tools could improve ERCP training by selecting the most appropriate cases for hands-on training, with the aim of increasing patient safety.
Tough Porous Silk Nanofiber‐Derived Cryogels with Osteogenic and Angiogenic Capacity for Bone Repair
Authors: Jianwen Hou, Zhaozhao Ding, Xin Zheng, Yixin Shen, Qiang Lu, David L Kaplan
Journal: Advanced Healthcare Materials (2023)

Tough porous cryogels with angiogenesis and osteogenesis features remain a design challenge for utility in bone regeneration. Here, building off of the recent efforts to generate tough silk nanofiber-derived cryogels with osteogenic activity, deferoxamine (DFO) is loaded in silk nanofiber-derived cryogels to introduce angiogenic capacity. Both the mechanical cues (stiffness) and the sustained release of DFO from the gels are controlled by tuning the concentration of silk nanofibers in the system, achieving a modulus above 400 kPa and slow release of the DFO over 60 days. The modulus of the cryogels and the released DFO induce osteogenic and angiogenic activity, which facilitates bone regeneration in vivo in femur defects in rat, resulting in faster regeneration of vascularized bone tissue. The tunable physical and chemical cues derived from these nanofibrous-microporous structures support the potential for silk cryogels in bone tissue regeneration.
Skin γδ T cell inflammatory responses are hardwired in the thymus by oxysterol sensing via GPR183 and calibrated by dietary cholesterol
Authors: Michela Frascoli, Enxhi Ferraj, Bing Miu, Justin Malin, Nicholas A. Spidale, Jennifer Cowan, Susannah C. Shissler, Robert Brink, Ying Xu, Jason G. Cyster, Avinash Bhandoola, Joonsoo Kang, Andrea Reboldi
Journal: Immunity (2023)
Understanding human health through metatranscriptomics
Authors: Teija Ojala, Esko Kankuri, Matti Kankainen
Journal: Trends in Molecular Medicine (2023)

Metatranscriptomics has revolutionized our ability to explore and understand transcriptional programs in microbial communities. Moreover, it has enabled us to gain deeper and more specific insight into the microbial activities in human gut, respiratory, oral, and vaginal communities. Perhaps the most important contribution of metatranscriptomics arises, however, from the analyses of disease-associated communities. We review the advantages and disadvantages of metatranscriptomics analyses in understanding human health and disease. We focus on human tissues low in microbial biomass and conditions associated with dysbiotic microbiota. We conclude that a more widespread use of metatranscriptomics and increased knowledge on microbe activities will uncover critical interactions between microbes and host in human health and provide diagnostic basis for culturing-independent, direct functional pathogen identification.
Update on the treatment of idiopathic hypersomnia: Progress, challenges, and expert opinion
Authors: Isabelle Arnulf, Robert Thomas, Asim Roy, Yves Dauvilliers
Journal: Sleep Medicine Reviews (2023)

Idiopathic hypersomnia is a central hypersomnolence disorder of unknown origin characterized by excessive daytime sleepiness despite normal or long sleep time, and frequent severe sleep inertia. Management strategies have been largely derived from expert consensus, due to a lack of disease-specific assessments and reliance on case series and rare randomized controlled studies. Guidelines recommend treatment with off-label medications. Modafinil, which was approved for idiopathic hypersomnia until 2011 in Europe, is the most commonly used treatment and improved sleepiness in two recent randomized placebo-controlled trials. In 2021, low-sodium oxybate (LXB) was approved in the United States for idiopathic hypersomnia. In a placebo-controlled, double-blind, randomized withdrawal study, LXB reduced daytime sleepiness and sleep inertia, and improved daily functioning. Here, treatment options are reviewed considering the authors' professional experience, current guidelines, and the latest research developments. The choice of pharmacotherapy should be guided by symptom profile, age, comorbidities (eg, depressive symptoms, cardiovascular problems), and concomitant medications (eg, oral contraceptives). Nonpharmacologic approaches have a role in management. An instrument (idiopathic hypersomnia severity scale) has been validated in idiopathic hypersomnia specifically, opening a path to better assessment of symptoms, impact, and response to treatment. Continued research on idiopathic hypersomnia is needed to support treatment algorithms.
Intramuscular Hemangioma
Authors: Amram J. Cohen
Journal: JAMA (1983)

In two cases of intramuscular hemangioma of the paraspinous muscles, the tumors were treated with arteriographic embolization followed by immediate local excision. We found that this technique creates a hypovascular surgical field and facilitates the dissection. We believe this approach will decrease morbidity and potential mortality. (<i>JAMA</i>1983;249:2680-2682)
Engineering Inflammation‐Resistant Cartilage: Bridging Gene Therapy and Tissue Engineering
Authors: Angela Bonato, Philipp Fisch, Simone Ponta, David Fercher, Mikko Manninen, Daniel Weber, Kari K. Eklund, Goncalo Barreto, Marcy Zenobi‐Wong
Journal: Advanced Healthcare Materials (2023)

Abstract Articular cartilage defects caused by traumatic injury rarely heal spontaneously and predispose into post‐traumatic osteoarthritis. In the current autologous cell‐based treatments the regenerative process is often hampered by the poor regenerative capacity of adult cells and the inflammatory state of the injured joint. The lack of ideal treatment options for cartilage injuries motivated the authors to tissue engineer a cartilage tissue which would be more resistant to inflammation. A clustered regularly interspaced short palindromic repeats (CRISPR)‐Cas9 knockout of TGF‐ β ‐activated kinase 1 ( TAK1 ) gene in polydactyly chondrocytes provides multivalent protection against the signals that activate the pro‐inflammatory and catabolic NF‐ κ B pathway. The TAK1 ‐KO chondrocytes encapsulate into a hyaluronan hydrogel deposit copious cartilage extracellular matrix proteins and facilitate integration onto native cartilage, even under proinflammatory conditions. Furthermore, when implanted in vivo, compared to WT fewer pro‐inflammatory M1 macrophages invade the cartilage, likely due to the lower levels of cytokines secreted by the TAK1 ‐KO polydactyly chondrocytes. The engineered cartilage thus represents a new paradigm‐shift for the creation of more potent and functional tissues for use in regenerative medicine.
Dually Crosslinked Copper‐Poly(tannic acid) Nanoparticles with Microenvironment‐Responsiveness for Infected Wound Treatment
Authors: Dongying Li, Jiarun Li, Siwei Wang, Qinmei Wang, Wei Teng
Journal: Advanced Healthcare Materials (2023)

Abstract Reducing the burden of death due to wound infection is an urgent global public health priority. Metal‐phenolic networks (MPNs) have received widespread attention in antimicrobial infections due to their facile synthesis process, excellent biocompatibility, and antimicrobial properties brought about by polyphenols and metal ions. However, typical therapeutic MPNs show rapid release of metal ions due to their poor solution stability, impeding long‐acting efficacy in multiple wound healing stages. To address these issues, copper‐poly (tannic acid) nanoparticles (Cu‐PTA NPs): robust (dually crosslinked), microenvironment‐responsive, antibacterial, antioxidative, and anti‐inflammatory are prepared, which hierarchically modulate the infected wound healing process. Covalently polymerized via phenol‐formaldehyde condensation and crosslinked with bioactive Cu 2+ , reactive polyphenols are preserved, and Cu 2+ is efficiently entrapped in the PTA scaffold. The proposed strategy relieves the systemic toxicity, and only high reactive oxygen species (ROS)level as stimuli can “turn on” the catalytic activity of Cu 2+ to implement antibacterial therapy specifically in an infected wound. Systematic tissue regeneration assessment on the infected full‐thickness skin wounds of rats demonstrates enhanced wound healing rate. Cu‐PTA NPs enables the direct application in infected wound and exertion of long‐acting healing efficacy. This synergetic therapy strategy will pave the way for more complicated infections and inflammatory diseases.
Assessing Long-term Treatment Benefits Using Complementary Statistical Approaches: An In Silico Analysis of the Phase III Keynote-045 and Checkmate-214 Immune Checkpoint Inhibitor Trials
Authors: Ana Cavillon, Damien Pouessel, Nadine Houédé, Fanny Mathevet, Jean Yves Dauxois, Christine Chevreau, Stéphane Culine, Jean-Pierre Delord, Raphael Porcher, Thomas Filleron
Journal: European Urology (2023)
Sarcopenia Among Patients With Nonalcoholic Fatty Liver Disease (NAFLD) Is Associated With Advanced Fibrosis
Authors: Michael Harring, Pegah Golabi, James M. Paik, Dipam Shah, Andrei Racila, Rebecca Cable, Manirath Srishord, Zobair M. Younossi
Journal: Clinical Gastroenterology and Hepatology (2023)
Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies
Authors: Q. Gao, Y.P. Lin, B.S. Li, G.Q. Wang, L.Q. Dong, B.Y. Shen, W.H. Lou, W.C. Wu, D. Ge, Q.L. Zhu, Y. Xu, J.M. Xu, W.J. Chang, P. Lan, P.H. Zhou, M.J. He, G.B. Qiao, S.K. Chuai, R.Y. Zang, T.Y. Shi, L.J. Tan, J. Yin, Q. Zeng, X.F. Su, Z.D. Wang, X.Q. Zhao, W.Q. Nian, S. Zhang, J. Zhou, S.L. Cai, Z.H. Zhang, J. Fan
Journal: Annals of Oncology (2023)
International Liver Cancer Association (ILCA) white paper on hepatocellular carcinoma risk stratification and surveillance
Authors: Amit G. Singal, Marco Sanduzzi-Zamparelli, Pierre Nahon, Maxime Ronot, Yujin Hoshida, Nicole Rich, Maria Reig, Valerie Vilgrain, Jorge Marrero, Josep M. Llovet, Neehar D. Parikh, Augusto Villanueva
Journal: Journal of Hepatology (2023)
Perspectives on complement and phagocytic cell responses to nanoparticles: From fundamentals to adverse reactions
Authors: S. Moein Moghimi, Hajira B. Haroon, Anan Yaghmur, A. Christy Hunter, Emanuele Papini, Z. Shadi Farhangrazi, Dmitri Simberg, Panagiotis N. Trohopoulos
Journal: Journal of Controlled Release (2023)

The complement system, professional phagocytes and other cells such as Natural killer cells and mast cells are among the important components of the innate arm of the immune system. These constituents provide an orchestrated array of defences and responses against tissue injury and foreign particles, including nanopharmaceuticals. While interception of nanopharmaceuticals by the immune system is beneficial for immunomodulation and treatment of phagocytic cell disorders, it is imperative to understand the multifaceted mechanisms by which nanopharmaceuticals interacts with the immune system and evaluate the subsequent balance of beneficial versus adverse reactions. An example of the latter is adverse infusion reactions to regulatory-approved nanopharmaceuticals seen in human subjects. Here, we discuss collective opinions and findings from our laboratories in mapping nanoparticle-mediated complement and leucocyte/macrophage responses.
Ionizable drug delivery systems for efficient and selective gene therapy
Authors: Yu-Qi Zhang, Ran-Ran Guo, Yong-Hu Chen, Tian-Cheng Li, Wen-Zhen Du, Rong-Wu Xiang, Ji-Bin Guan, Yu-Peng Li, Yuan-Yu Huang, Zhi-Qiang Yu, Yin Cai, Peng Zhang, Gui-Xia Ling
Journal: Military Medical Research (2023)

Abstract Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function. However, a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells. To be excited, the development of ionizable drug delivery systems (IDDSs) has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019 (COVID-19) in 2021. Compared with conventional cationic gene vectors, IDDSs can decrease the toxicity of carriers to cell membranes, and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures. Despite the progress, there remain necessary requirements for designing more efficient IDDSs for precise gene therapy. Herein, we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms. The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of pDNA and four kinds of RNA. In particular, organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity. We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future, and indicate ideas for developing next generation gene vectors.
Increasing incidence and severity of invasive Group A streptococcal disease in Spanish children in 2019–2022
Authors: Elvira Cobo-Vázquez, David Aguilera-Alonso, Jaime Carrasco-Colom, Cristina Calvo, Jesús Saavedra-Lozano, Cristina Calvo, Isabel Mellado, David Grandioso, Jesús Saavedra-Lozano, David Aguilera-Alonso, Elena Rincón, Ana Jové, Emilia Cercenado, Francisco José Sanz Santaeufemia, María José Gónzalez, Elena Sánchez, Daniel Blázquez, Ángela Manzanares, Rut Del Valle, Elvira Cobo, Gloria Caro, Lucía Figueroa, Marta Llorente, Pilar Galán, Arantxa Berzosa, Marta Illán, Jaime Carrasco, Anabel Piqueras, Manuel Oltra, Victoria Rello, Mayli Lung, Anna Gamell, Nuria López, Borja Guarch, Anna Hernández, Montse Ruíz, Lourdes García, Lola Falcón, Leticia Martínez, Laura Martín, Begoña Carazo, María Sánchez-Códez, Almudena Alonso, Eloisa Cervantes, Ana Menasalvas, Genoveva Yagüe, Laura Calle, Elena Colino, Javier Cuenca, Beatriz Jiménez, Marta Pareja, Elena del Castillo
Journal: The Lancet Regional Health - Europe (2023)
Cholestasis impairs gut microbiota development and bile salt hydrolase activity in preterm neonates
Authors: Lauren E. Lynch, Amy B. Hair, Krishnakant G. Soni, Heeju Yang, Laura A. Gollins, Monica Narvaez-Rivas, Kenneth D. R. Setchell, Geoffrey A. Preidis
Journal: Gut Microbes (2023)

Cholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops in extreme prematurity and how cholestasis alters this maturation, we conducted a nested case-control study collecting 124 stool samples longitudinally from 24 preterm infants born at mean 27.2 ± 1.8 weeks gestation and 946 ± 249.6 g, half of whom developed physiologic cholestasis. Samples were analyzed by whole metagenomic sequencing, in vitro BSH enzyme activity assays optimized for low biomass fecal samples, and quantitative mass spectrometry to measure the bile acid metabolome. In extremely preterm neonates, acquisition of the secondary bile acid biosynthesis pathway and BSH genes carried by Clostridium perfringens are the most prominent features of early microbiome development. Cholestasis interrupts this developmental pattern. BSH gene abundance and enzyme activity are profoundly reduced in cholestatic neonates, resulting in decreased quantities of unconjugated bile acids. UDCA restores total fecal bile acid levels in cholestatic neonates, but this is due to a 522-fold increase in fecal UDCA. A majority of bile acids in early development are atypical positional and stereo-isomers of bile acids. We report novel associations linking isomeric bile acids and BSH activity to neonatal growth trajectories. These data highlight deconjugation of bile acids as a key microbial function that is acquired in early neonatal development and impaired by cholestasis.
The emerging roles of bacterial proteases in intestinal diseases
Authors: Alberto Caminero, Mabel Guzman, Josie Libertucci, Alan E. Lomax
Journal: Gut Microbes (2023)

Proteases are an evolutionarily conserved family of enzymes that degrade peptide bonds and have been implicated in several common gastrointestinal (GI) diseases. Although luminal proteolytic activity is important for maintenance of homeostasis and health, the current review describes recent advances in our understanding of how overactivity of luminal proteases contributes to the pathophysiology of celiac disease, irritable bowel syndrome, inflammatory bowel disease and GI infections. Luminal proteases, many of which are produced by the microbiota, can modulate the immunogenicity of dietary antigens, reduce mucosal barrier function and activate pro-inflammatory and pro-nociceptive host signaling. Increased proteolytic activity has been ascribed to both increases in protease production and decreases in inhibitors of luminal proteases. With the identification of strains of bacteria that are important sources of proteases and their inhibitors, the stage is set to develop drug or microbial therapies to restore protease balance and alleviate disease.
Circulating androgen regulation by androgen-catabolizing gut bacteria in male mouse gut
Authors: Tsun-Hsien Hsiao, Chia-Hong Chou, Yi-Lung Chen, Po-Hsiang Wang, Guo-Jie Brandon-Mong, Tzong-Huei Lee, Tien-Yu Wu, Po-Ting Li, Chen-Wei Li, Yi-Li Lai, Yu-Lin Tseng, Chao-Jen Shih, Po-Hao Chen, Mei-Jou Chen, Yin-Ru Chiang
Journal: Gut Microbes (2023)

Abnormally high circulating androgen levels have been considered a causative factor for benign prostatic hypertrophy and prostate cancer in men. Recent animal studies on gut microbiome suggested that gut bacteria are involved in sex steroid metabolism; however, the underlying mechanisms and bacterial taxa remain elusive. Denitrifying betaproteobacteria Thauera spp. are metabolically versatile and often distributed in the animal gut. Thauera sp. strain GDN1 is an unusual betaproteobacterium capable of catabolizing androgen under both aerobic and anaerobic conditions. We administered C57BL/6 mice (aged 7 weeks) with strain GDN1 through oral gavage. The strain GDN1 administration caused a minor increase in the relative abundance of Thauera (≤0.1%); however, it has profound effects on the host physiology and gut bacterial community. The results of our ELISA assay and metabolite profile analysis indicated an approximately 50% reduction in serum androgen levels in the strain GDN1-administered male mice. Moreover, androgenic ring-cleaved metabolites were detected in the fecal extracts of the strain GDN1-administered mice. Furthermore, our RT – qPCR results revealed the expression of the androgen catabolism genes in the gut of the strain GDN1-administered mice. We found that the administered strain GDN1 regulated mouse serum androgen levels, possibly because it blocked androgen recycling through enterohepatic circulation. This study discovered that sex steroids serve as a carbon source of gut bacteria; moreover, host circulating androgen levels may be regulated by androgen-catabolizing gut bacteria. Our data thus indicate the possible applicability of androgen-catabolic gut bacteria as potent probiotics in alternative therapy of hyperandrogenism.
Methodological challenges in neonatal microbiome research
Authors: Jonathan A Chapman, Christopher J Stewart
Journal: Gut Microbes (2023)

Following microbial colonization at birth, the gut microbiome plays a vital role in the healthy development of human neonates and impacts both health and disease in later life. Understanding the development of the neonatal gut microbiome and how it interacts with the neonatal host are therefore important areas of study. However, research within this field must address a range of specific challenges that impact the design and implementation of research methods. If not considered ahead of time, these challenges have the potential to introduce biases into studies, negatively affecting the relevance, reproducibility, and impact of any findings. This review outlines the nature of these challenges and points to current and future solutions, as outlined in the literature, to assist researchers in the early stages of study design.